The objectives of the program are to identify, isolate and characterize the action of non-histone chromosomal proteins influencing tumor growth using transplanted hepatomas as a model system. It is proposed to study the influence of growth regulating drugs on the metabolism of non-histone chromosomal proteins. The relationship of protein synthesis and metabolism to growth rate will be compared in liver and hepatomas. Proteins will be obtained from purified nuclei by saline extraction and will be further resolved by isoelectric focusing. Purification will be attempted of non-histone chromosomal proteins whose concentration appears related to growth rate. Particular attention will be directed to proteins subject to phosphorylation and correlations between phosphate content and turnover and the rate of cell division will be investigated. In order to test the growth regulatory properties of isolated proteins, their influence on cellular proliferation will be examined after their administration as exogenous agents to cells in culture. BIBLIOGRAPHIC REFERENCES: M.A. Lea, M.R. Koch and H.P. Morris. Nuclear protein changes in rat hepatomas correlating with growth rate. Cancer Res. 35, 1693-1697 (1975). M.A. Lea, M.R. Koch and H.P. Morris. Tumor-selective inhibition of the incorporation of H3-labeled amino acids into protein by cyanate. Cancer Res. 35, 2321-2326 (1975).